Knee articular cartilage damage in osteoarthritis: analysis of MR image biomarker reproducibility in ACRIN-PA 4001 multicenter trial

Abstract

Purpose: To prospectively determine the reproducibility of quantitative magnetic resonance (MR) imaging biomarkers of the morphology and composition (spin lattice relaxation time in rotating frame [T1-ρ], T2) of knee cartilage in a multicenter multivendor trial involving patients with osteoarthritis (OA) and asymptomatic control subjects.

Materials and methods: This study was HIPAA compliant and approved by the institutional review committees of the participating sites, with written informed consent obtained from all participants. Fifty subjects from five sites who were deemed to have normal knee joints (n = 18), mild OA (n = 16), or moderate OA (n = 16) on the basis of Kellgren-Lawrence scores were enrolled. Each participant underwent four sequential 3-T knee MR imaging examinations with use of the same imager and with 2-63 days (median, 18 days) separating the first and last examinations. Water-excited three-dimensional T1-weighted gradient-echo imaging, T1-ρ imaging, and T2 mapping of cartilage in the axial and coronal planes were performed. Biomarker reproducibility was determined by using intraclass correlation coefficients (ICCs) and root-mean-square coefficients of variation (RMS CVs, expressed as percentages).

Results: Morphometric biomarkers had high reproducibility, with ICCs of 0.989 or greater and RMS CVs lower than 4%. The largest differences between the healthy subjects and the patients with radiographically detected knee OA were those in T1-ρ values, but precision errors were relatively large. Reproducibility of T1-ρ values was higher in the thicker patellar cartilage (ICC range, 0.86-0.93; RMS CV range, 14%-18%) than in the femorotibial joints (ICC range, 0.20-0.84; RMS CV range, 7%-19%). Good to high reproducibility of T2 was observed, with ICCs ranging from 0.61 to 0.98 and RMS CVs ranging from 4% to 14%.

Conclusion: MR imaging measurements of cartilage morphology, T2, and patellar T1-ρ demonstrated moderate to excellent reproducibility in a clinical trial network.

Figure 1:

ACRIN-PA 4001 flowchart: Only those subjects in whom four complete artifact-free protocol-compliant data sets were obtained were included in ICC determinations. Causes of data set exclusion were as follows: For morphometric measurements, 11 cases in the patella were excluded owing to incomplete data sets (†) (n = 3), wrong parameters (n = 2), and incomplete coverage (n = 6); and 12 cases in the femorotibial joint were excluded owing to incomplete data sets (n = 3), wrong parameters (n = 2), and incomplete coverage (n = 7). For T1-ρ measurements, in the patella 12 cases were excluded owing to parameter programming error at one site and three cases were excluded owing to artifact, two cases in the femorotibial joint were excluded owing to artifact, and one case in the lateral tibia was excluded owing to local susceptibility artifact. For T2 measurements, one case in the patella was excluded owing to a missing data point, six cases in the lateral compartment were excluded owing to missing data points (n = 2) and artifact (n = 4), and five cases in the medial compartment were excluded owing to missing data points (n = 2) and artifact (n = 3). cLF = central lateral femoral condyle, cMF = central (weight-bearing) medial femoral condyle, KOOS = knee osteoarthritis outcome score, LT = lateral tibia, MT = medial tibia, P = patella.

Figure 2a:

Representative ROIs for (a) lateral and (b) medial compartments of femorotibial joint used in analysis of cartilage T2. ROI was limited to center section of coronal multisection multiecho source images. Orange indicates tibial ROIs, and blue indicates femoral ROIs. cLF = central lateral femoral condyle, cMF = central (weight-bearing) medial femoral condyle, LT = lateral tibia, MT = medial tibia.

Figure 2b:

Representative ROIs for (a) lateral and (b) medial compartments of femorotibial joint used in analysis of cartilage T2. ROI was limited to center section of coronal multisection multiecho source images. Orange indicates tibial ROIs, and blue indicates femoral ROIs. cLF = central lateral femoral condyle, cMF = central (weight-bearing) medial femoral condyle, LT = lateral tibia, MT = medial tibia.